Blood:中性粒细胞外网状陷阱促进COVID-19急性呼窘患者形成免疫血栓

2020-07-08 MedSci原创 MedSci原创

新型NET抑制因子(nNIF)可阻断由COVID-19血浆诱导的NET,代表了对COVID-19的潜在治疗干预。

中心点:

COVID-19 ARDS中,中性粒细胞外网状陷阱(NETs)通过血小板-中性粒细胞相互作用导致微血栓形成。新型NET抑制因子(nNIF)可阻断由COVID-19血浆诱导的NET,代表了对COVID-19的潜在治疗干预。

摘要:

目前,全球COVID-19感染者已逾千万,临床表现多样,从单纯性血栓形成到需要呼吸机支持的急性呼吸窘迫综合征(ARDS)。中性粒细胞外网状陷阱(NETs)是由中性粒细胞坏死或者凋亡后染色体解旋消融形成一种特殊的结构,细胞质膜保持完整,可固定捕杀病原体,并可触发免疫血栓形成。

Middleton等开展了一项COVID-19患者(n=33)的回顾性队列研究,以年龄和性别匹配的非COVID-19患者(n=17)为对照,以研究NET和COVID-19严重程度和进展之间的相关性。

研究人员检测了血浆髓过氧化物酶 (MPO)-DNA复合物(NET)、血小板因子4、RANTES和部分细胞因子,并检测了3例COVID-19肺尸检的NET和血小板受累情况。研究人员还评估了COVID-19患者的中性粒细胞和与COVID-19血浆孵育的健康人的中性粒细胞的NET形成,同时还检测了新型NET抑制因子(nNIF)封闭COVID-19血浆诱导的NET形成的能力。

进行气管插管和死亡结局的COVID-19患者的血浆MPO-DNA复合物增多。疾病严重程度与血浆MPO-DNA复合物直接相关,而PaO2/FiO2与之负相关。在确认有包含微血栓的NET和中性粒-血小板浸润的肺活检COVID-19中,触发NET的可溶性细胞因子显著增加。最后,在体外起始时,COVID-19中性粒细胞形成过多的NET,COVID-19血浆触发的NET形成可被nNIF阻断。

综上,NET触发免疫血栓形成可能部分解释了COVID-19患者血栓形成前的临床表现,NETs可能作为治疗干预的靶点。

原始出处:

Elizabeth A Middleton,et al. Neutrophil Extracellular Traps (NETs) Contribute to Immunothrombosis in COVID-19 Acute Respiratory Distress Syndrome. Blood. June 29, 2020.

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    2020-10-25 yese
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    2020-07-20 gq1688888

    视频

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    2020-07-09 曹译匀

    共同战疫!

    0

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